The Macrophage Galactose-Type Lectin Can Function as an Attachment and Entry Receptor for Influenza Virus

Ng, Wendy; Liong, Stella; Tate, Michelle D.; Irimura, Tatsuro; Denda-Nagai, Kaori; Brööks, Andrëw G.; Londrigan, Sarah L.; Reading, Patrick C.

doi:10.1128/jvi.02014-13

Cited by 44 publications

(43 citation statements)

References 66 publications

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“…Glycosylation of IAV HA is a critical factor modulating the ability of C-type lectin receptors (CLR) to recognize different IAV. Highly glycosylated strains infect murine M⌽ more efficiently, and infection is blocked by multivalent ligands of CLR such as mannan and asialofetuin (ASF) (6)(7)(8). We aimed to generate genetically defined viruses that differed only in their HA gene, such that one expressed the HA of the highly glycosylated H1N1 strain A/Brazil/ 11/78 (Braz; H1N1, four potential glycosylation sites on the head of HA) and the other expressed the HA of the H1N1 strain A/Puerto Rico/8/34 (PR8; H1N1), which lacks glycosylation sites on the head of HA.…”

Section: Resultsmentioning

confidence: 99%

“…M⌽ and epithelial cells were infected with IAV, and the percentage of IAV-infected cells was determined as described previously (8,14). Unless stated otherwise, the cells were incubated with 10 6 PFU of IAV (representing a multiplicity of infection [MOI] of 5 PFU/ cell) in serum-free medium for 1 h at 37°C.…”

Section: Virus Infection Assaysmentioning

confidence: 99%

“…Our recent studies identified the M⌽ mannose receptor (MMR) and M⌽ galactose-type lectin-1 (MGL1) as attachment and entry receptors for IAV. Glycans expressed on the HA and neuraminidase (NA) surface glycoproteins of IAV are recognized by MMR and/or MGL1, promoting infectious entry into mouse M⌽ (6)(7)(8). However, the mouse-virulent A/Puerto Rico/9/34 (PR8; H1N1 subtype) strain is poorly glycosylated and not recog-nized efficiently by either receptor, consistent with its limited capacity to infect mouse M⌽ in vitro (6,7,9).…”

mentioning

confidence: 99%

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Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

Londrigan

Short

et al. 2015

J Virol

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Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (M⌽) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of M⌽ is impaired or the extent to which seasonal IAV replicate in M⌽. Herein, we compared mouse M⌽ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse M⌽. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected M⌽, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAIreplicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. In humans, infection with seasonal influenza A viruses (IAV) is generally restricted to the respiratory tract. IAV infection of airway epithelial cells (AEC) is initiated following recognition of cell surface sialic acid (SIA) by the viral hemagglutinin (HA) glycoprotein (reviewed in reference 1). In addition to HA-SIA binding, it is likely that particular membrane-associated glycoproteins and/or glycolipids facilitate virus entry into AEC; however, the identity of such an entry receptor(s) is currently unknown. IAV infection of AEC results in productive virus replication, characterized by synthesis of viral RNA (vRNA) and mRNA, production of viral proteins, virion assembly, and budding of viral progeny from the surfaces of infected cells. Productive infection of AEC results in amplification of IAV in the airways, promoting virus dissemination and disease.In addition to AEC, macrophages (M⌽) are one of the first cells in the respiratory tract to detect and respond to IAV. As for AEC, binding ...

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Section: Resultsmentioning

confidence: 99%

Section: Virus Infection Assaysmentioning

confidence: 99%

mentioning

confidence: 99%

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Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

Londrigan

Short

et al. 2015

J Virol

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“…In contrast, mouse PEC macrophages and bronchoalveolar lavage (BAL) macrophages that predominantly express a2,6-linked sialic acid receptors show poor susceptibility to infection with a PR8 IAV strain that binds preferentially to a2,3-linked sialic acids [11,28,41]. Variability in the receptor-binding preference of PR8 viruses of different origins has been reported, with the PR8 Warwick strain binding equally well to a2,3-linked and a2,6-linked receptors [42].…”

Section: Mechanism Of Iav Restriction In Macrophagesmentioning

confidence: 99%

“…Glycosylation of the HA protein may impact on the ability of the virus to interact efficiently with C-type lectins, such as the mannose receptor and the galactose-type lectin, which, in addition to sialic acid receptors, act as attachment and entry receptors for IAVs [41,[43][44][45]. In support of this hypothesis, IAV infection of macrophages with RG-Braz-HA in the presence of mannan or asialofetuin, which have been shown to block Ctype lectin interactions, is reduced to levels similar to that of PR8 [27].…”

Section: Mechanism Of Iav Restriction In Macrophagesmentioning

confidence: 99%

Influenza virus replication in macrophages: balancing protection and pathogenesis

Cline

Beck

Bianchini

2017

Journal of General Virology

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Macrophages are essential for protection against influenza A virus infection, but are also implicated in the morbidity and mortality associated with severe influenza disease, particularly during infection with highly pathogenic avian influenza (HPAI) H5N1 virus. While influenza virus infection of macrophages was once thought to be abortive, it is now clear that certain virus strains can replicate productively in macrophages. This may have important consequences for the antiviral functions of macrophages, the course of disease and the outcome of infection for the host. In this article, we review findings related to influenza virus replication in macrophages and the impact of productive replication on macrophage antiviral functions. A clear understanding of the interactions between influenza viruses and macrophages may lead to new antiviral therapies to relieve the burden of severe disease associated with influenza viruses.

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The innate and adaptive immune response to avian influenza virus

Vervelde

Kapczynski

2016

Animal Influenza

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The Macrophage Galactose-Type Lectin Can Function as an Attachment and Entry Receptor for Influenza Virus

Cited by 44 publications

References 66 publications

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

Influenza virus replication in macrophages: balancing protection and pathogenesis

The innate and adaptive immune response to avian influenza virus

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